Innate Immunity Cellular Responses

Introduction

Macrophage

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• If pathogens breach the barriers formed by the skin and mucus membranes, they must be detected and destroyed by cellular and humoral means
• The cells involved with innate protection are:
  • Blood granulocytes, or Polymorphonuclear Cells
    • Notable for their multi-lobed nuclei
    • Neutrophils: phagocytose bacteria
    • Eosinophils: kill parasites by the release of granules
    • Basophils/ mast cells: kill parasites by the release of granules
  • Blood monocytes: phagocytose bacteria
  • Tissue mast cells and macrophages: phagocytose bacteria
• Effectively, innate cellular response seeks to hold off the infection until the adaptive response can back it up with a more specific attack

Macrophages

Monocytes - J. Bredl, RVC 2008

• The role of macrophages in Innate Immunity is to act as primary phagocytes
• Macrophages are present within tissues and take the form of distinct, tissue-specific populations:
  • Alveolar macrophages
  • Tissue histiocytes
  • Glomerular macrophages
  • Hepatic Küpffer cells
  • CNS microglia
  • Sinus-lining macrophages of the lymph nodes and spleen
• Monocytes (immature macrophages) are circulating phagocytes
  • Circulate for 6-8 hours
  • Can function as phagocytes within the blood and as newly migrated cells in tissues
  • Chiefly function to replace the various tissue macrophage populations

Neutrophils

Neutrophils - J. Bredl, RVC 2008

• Neutrophils are the principal, highly active phagocytes in the blood
  • Comprise 30-70% of white blood cells depending on species
  • Kill and digest microbes in a similar way as macrophages
• Neutrophils can also cause extracellular bacterial killing by disrupting bacterial membranes
  • Secrete small antibacterial peptides
    • E.g. defensins and bactenecins
• Neutrophils produce vasoactive peptides
  • E.g. histamine and bradykinin
  • Cause a great increase in extravasation of blood granulocytes and monocytes and plasma proteins at the site of infection
• Neutrophils are the archetypal cell associated with acute inflammation
  • Are attracted to sites of inflammation by:
    • Complement activation
    • Cytokine production
    • Changes to vascular endothelium
  • Neutrophil activation in an inflammatory lesion results in the release of prostaglandins
    • Responsible for vasoactive changes and for pain
• The accumulation of dead and dying neutrophils at the site of infection is called pus
  • Their removal from the site after the removal of infection is an important step in the resolution of the lesion

Eosinophils

Eosinophil - J. Bredl, RVC 2008

• Eosinophils are less common than neutrophils, and they are not phagocytic
  • Make up <5% of the leukocytes in normal blood
• Eosinophil numbers are increased:
  • Slightly during the resolution phase of inflammation
  • Many-fold in parasite-infected animals
    • The presence of a large proportion of eosinophils in a blood smear is highly indicative of parasitaemia
• Mainly function by targeting the surface of parasites by means of specific antibody or complement
  • Release a large range of toxic molecules that break down the parasite integument
• Prominent in allergic (anaphylactic) reactions

Basophils / Mast Cells

Basophil - J. Bredl, RVC 2008

• Basophils/mast cells are principally localised at epithelial surfaces
  • Very small numbers are present in blood
    • Less than 0.5% circulating leukocytes
• They have two principal functions:
  1. Induction of acute inflammation
     • Trauma and/ or bacterial infection causes the production of cytokines by the mast cells that induce a classical acute inflammatory response
  2. Response to parasite infection
     • Specific IgE binds cells
     • Subsequent contact with antigen causes the mast cells to degranulate
     • Release enzymes and vasoactive substances that can result in a high level of mucus secretion and smooth muscle contraction
• Also produce factors that influence local host cell physiology
  • Various mediators increase the ratio of phagocyte to microbe

Originally funded by the RVC Jim Bee Award 2007